Streptococcus mutans is the major etiologic agent responsible for Dental caries, the most prevalent disease in developed and developing countries. Most clinical isolates of S. mutans produce antimicrobial peptides called mutacins. Mutacins are active against a wide spectrum of Gram-positive bacteria, including pathogens and oral commensals. Production of mutacin is under the control of the same regulatory networks involved with stress response, quorum sensing, competence development and biofilm formation. Thus the production of mutacin may play a double role: it may give the producer strain a competitive edge in gaining dominance in the Dental plaque, leading to Dental caries, at the same time, it may protect the human host from Gram-positive bacterial infections. The proposed research Aims to study the genetic, biochemical and biological aspects of mutacin production with the following approaches: Specific Aim 1, to elucidate the mechanism of regulation for mutacin production. Specific Aim 2, to develop mutacin into a future antimicrobial drug. The proposed research will have a significant impact on two fronts. The first front is the alarming surge in resistance to the existing battery of antibiotics among emerging and existing bacterial pathogens, and the increasing threat of bio-terrorist attack using genetically engineered anthrax pathogens resistant to all existing antibiotics. These threats underpin the importance and urgency of finding unconventional antibiotics, to which resistance has not been developed. The second front is understanding the mechanism of gene regulation in S. mutans during stress response and biofilm formation. This knowledge will help design effective measures to control the growth and virulence of S. mutans in the Dental plaque.